Use of clotrimazole to treat herpes labialis

ABSTRACT

Warm-blooded animals are treated for Herpes Simplex Virus-I by administering to the animal a dosage, effective to alleviate the symptoms of the virus, of Clotrimazole (chemically called 1-(o-chloro-α, α-diphenylbenzyl) imidazole) and at least one pharmaceutically acceptable carrier, wherein the compound is in the range of from about 0.01 to about 95% by weight of the composition.

BACKGROUND OF THE INVENTION

This invention relates to a method of treating Herpes Simplex Virus-I(called herpes I) infections of the labial area in mammals and moreparticularly to a method of treating herpes I infections of the labialarea in mammals with an antiviral composition containing Clotrimazole(chemically called 1-(o-chloro-α,α-diphenylbenzyl) imidazole), or itssalts, and at least one pharmaceutically accepted carrier.

Herpes Labialis is an acute and recurring painful vesicular eruption ofthe oral mucosa in the vermilion borders of the lips. The causativeagent is herpes virus, type I, and the initial infection usually occursin childhood. Mild trauma such as sunburn, chapping, or fever may be apredisposing factor for a recurrent eruption; the common name for thelesion is a "cold sore".

The onset of a recurrent lesion is usually a feeling of fullness with aburning or itching sensation on the lips. This occurs before the typicalvesicle develops. Vesicular lesions usually exist for several hoursbefore the vesicle breaks or the fluid becomes secondarily infected. Thelesions then become yellowish and crusted. The condition is selflimiting, symptoms generally subsiding after from about 7 to 10 days.

No prior art is known which discloses the use of Clotrimazole for thetreatment of herpes I.

SUMMARY OF THE INVENTION

This invention is directed to a method of treating herpes I infectionsof the labial area in mammals comprising administering to the mammal inneed of said treatment an effective amount for treating the herpes Ivirus of a composition of Clotrimazole or its salts and at least onepharmaceutically acceptable carrier, wherein the compound is from about0.01 to about 95% by weight of the composition.

DETAILED DESCRIPTION OF THE INVENTION

The Clotrimazole drug of this invention can be administered in theantiviral treatment according to this invention by any means thateffects contact of the active ingredient compound with the site of virusinfection in the body, after the infection sets in. The normal dosageform of the drug is topical application. The dosage form may be asolution, gel, emulsion, suspension, paste, ointment, powder, or othersuitable formulation. The dosage of the drug administered will bedependent upon the virus being treated, i.e. herpes I, weight of therecipient, the frequency of treatment, and the effect desired. Generallyin man, a daily topical dosage of active ingredient will be from about 5milligrams to about 50 milligrams per application, although lower andhigher amounts can be used. The active ingredient, the drug, can beemployed in useful compositions according to the present invention insuch dosage forms as solution, semisolid and solid form. These dosageforms preferrably deliver from about 5 milligrams to about 50 milligramsof active ingredient per application, with a range from about 10milligrams to about 25 milligrams per application being preferred. Inthese dosage forms the antiviral composition will contain at least onenon-toxic pharmaceutically acceptable carrier for the active ingredient.

Examples of the non-toxic carriers or adjuvants are viscosity enhancerssuch as bentonite, celluloses (e.g. methylcellulose, ethylcellulose, andcarboxy methylcellulose), polyvinylpyrrolidone (PVP), tragacanth,glyceryl monostearate, cetyl alcohol, stearyl alcohol, syntheticspermaceti, and stearic acid; pH modifiers such as dibasic sodiumphosphate, citric acid, and sodium hydroxide; preservatives such asmethylparaben, propylparaben, benzoic acid, and benzyl alcohol;stability enhancers such as sodium bisulfite and ascorbic acid; coloringsuch as food, drug and cosmetic (FD&C) and drug and cosmetic (D&C)colors certified by the Food and Drug Administration (FDA); solventssuch as water, alcohol (e.g. ethyl alcohol and isopropyl alcohol),polyethylene glycols, and propylene glycol; suspending agents such askaolin, celluloses (e.g. methylcellulose, ethylcellulose, and carboxymethylcellulose), acacia and tragacanth; emulsifying agents such asglyceryl stearate, decyloleate, cetearyl alcohol, polysorbate 60 andtriethanolamine; and humectants such as myristyl myristate.

Typical embodiments of the pharmaceutical composition of this inventionare as follows: (all percentages are by weight of composition)

    ______________________________________                                        Cream                                                                         Clotrimazole           0.05-10%                                               Sorbitan monostearate  1-20%                                                  Polysorbate 60         1-20%                                                  Cetyl esters wax       1-20%                                                  Cetostearyl alcohol    1-20%                                                  2-Octyl dodecanol      0.1-10%                                                Benzyl alcohol         0.1-5%                                                 Water                  1-80%                                                  Solution                                                                      Clotrimazole           0.05-20%                                               Polyethylene glycol 400                                                                              80-99.95%                                              ______________________________________                                    

EXAMPLE

The Clotrimazole was tested for its antiviral activity against herpes Iusing a method that was developed by Sidwell.

The hair was shaved from both sides of female guinea pigs. These femaleguinea pigs were then innoculated with the herpes I virus for producingthe lesions by spreading the virus over a measured area approximately 10millimeter square (mm²) and scratching within the area 10 timeshorizontally and 10 times vertically using an innoculating needle. Theguinea pigs were then divided up into groups of five per group. 15 hoursafter innoculation with the virus, the drug treatment was begun; thedrug was applied topically at the same dosage three times a day (TID)for six days. The drug was dissolved in a vanishing cream base at aconcentration of 10 mg. of drug per milliliter of vehicle. Each animalwas treated by applying the drug on the skin using three applicationsper lesion per treatment whereby each application delivered 0.15 gramsof solution containing 1.5 milligrams of clotrimazole; therefore eachdosage was approximately 4.5 milligrams. A placebo of the aqueoussolution (control) dosage was used in the same manner as mentioned aboveon a second group of guinea pigs. The animals were observed each day forthe six day period and the lesions, when visible, were measured andscored on the third day. In these experiments lesions were not observeduntil the second day after the drug treatment had begun. The third dayof observation is when the measurement was made and also showed theeffects of the drug treatment.

Calculations for antiviral activity of the drug are based on the averageof the average lesion size for the third day for each group of animals.The difference between the control group and the test group is termedthe reduction score which is a measure of the drug's antiviral activityand is expressed as percentage inhibition; the values are recorded inTable I.

The number of lesions recurring after the sixth day was also recorded inTable I.

                  TABLE I                                                         ______________________________________                                                Day 3         Day 6                                                           Mean Lesion                                                                            %        No. of New                                                                              %                                                 Size mm  Inhibition                                                                             Lesions   Inhibition                                ______________________________________                                        1%        18.9       17%      13      80%                                     Clotrimazole*                                                                 Vehicle Control                                                                         22.8       --       66      --                                      ______________________________________                                         *Clotrimazole is 1(ochloro-α, α-diphenylbenzyl) imidazole    

This data in Table I shows that on the third day when using a onepercent (1%) Clotrimazole cream the lesions are reduced in treatedanimals. With the Clotrimazole treatment only thirteen of the lesionsrecurred but with the control treatment 66 lesions did recur.

What is claimed:
 1. A method of treating herpes I infections of thelabial area in mammals comprising topically administering to the mammalin need of said treatment an effective amount for treating the herpes Ivirus of a composition of 1(o-chloro-α,α-diphenylbenzyl) imidazole orits salts and at least one pharmaceutically acceptable carrier, whereinthe compound is from about 0.01 to about 95% by weight of thecomposition.
 2. The method of claim 1 wherein the1(o-chloro-α,α-diphenylbenzyl) imidazole is dissolved at a 1%concentration in a homogeneous carrier of sorbitan monostearate,polyoxyethylene 20 sorbitan monostearate, cetyl esters wax, cetostearylalcohol, 2-octyl dodecanol, benzyl alcohol, and water.